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Testing Genes, Solving Little...

[2008-08-17 NY Times]

Testing Genes, Solving Little


August 16, 2008


It was supposed to be simple. Once it became cheap to scan large
numbers of people for large numbers of genetic differences, everyone
assumed that it would swiftly become straightforward to convert
genetic differences into physical differences — that we’d be able to
look at someone’s genome and say, this man is between 5-foot-10 and 6-
foot-2, has black hair, green eyes and a high risk of developing

Not so. The age of large-scale screening arrived about five years ago,
and a hunt for the genes underlying heritable human differences
immediately began. But with a few exceptions — almost all of which
predate the large screens — the business of genetic forecasting has
turned out to be much more difficult than anyone expected. And despite
the hype, the era of personal medicine — where your treatment is
tailored for your genes — remains frustratingly far away.

At the heart of this story there is a paradox. We have accumulated
huge databases on human genetic differences — but many of the
differences appear to be more or less irrelevant.

To see what I mean, suppose you set out to analyze a DNA sample from
someone you knew nothing about. What could you discover?

You could discover their sex. That’s easy. You could also discover
where they are from, genetically speaking. In the past five years, the
genetics of ancestry testing has become excellent. So much so that you
can reliably tell the difference between someone descended from
Swedes, as against Italians.

The reason this works is that in the past, humans didn’t move around
much. As a result, genetic differences accumulated slightly
differently in different groups. On average, then, Swedes’ genomes
resemble each other more closely than they resemble those of Italians
or American Indians.

If you discovered someone’s ancestors were Swedish, you’d infer that
they themselves are likely to be tall and blond with pale skin. But
that’s only because you already know what other Swedes look like. If
you didn’t — and this is the odd thing — you wouldn’t be able to infer
much from the genes themselves. This is because, by and large, we
don’t know how to translate genetic differences into physical

Consider height. This trait has a strong genetic component: we know
that as much as 90 percent of the difference in height between you and
me is because of differences in our genes. (The rest is because of
differences in things like nutrition.) One recent study, which looked
at more than 30,000 people, found 20 genes that influence height. But
together, these 20 genes accounted for just 3 percent of the
variation. That leaves a whopping 87 percent still to be accounted for.

Not all traits are so intractable. If your mystery individual had a
particular form of a gene known as melanocortin receptor 1, you’d know
they had red hair. A variant in the control region of another gene has
been strongly linked to blue eyes. Having variants of still another
gene greatly increases the odds of getting Alzheimer’s disease. Forms
of several genes have been strongly linked to adverse drug reactions —
or to a given drug having no effect at all. And then there are the
handful of genetic diseases we already knew about, like sickle cell
anemia and Huntington’s disease.

But for many traits, including diabetes, the pattern is similar to
what we see for height. Large numbers of people have been screened,
and impressively large numbers of genes have been implicated — but no
single gene seems to be having a particularly big effect by itself.
Moreover, and this is the more important point, a lot of the genetic
variation underlying each trait has not yet been found.

What does this mean? There are a couple of possibilities. Either, huge
numbers of genes affect most traits, with each gene making a tiny
contribution. If this is so, our hopes for finding meaningful risk
factors for most genetic diseases is poor. Or, variants of a few genes
do have a substantial effect but they are too rare to have been
discovered yet. (Most of the screens used today capture only the
500,000 most common genetic differences. Rare differences are
essentially invisible.) In which case, we need to change the way we
are approaching the problem.

Scientifically, this is fascinating. But from a practical point of
view, the results are discouraging. If you want to learn your odds of
getting different diseases, consult your family history. Or visit a
fortune teller. For most traits, genetic testing is — for now, anyway
— little better than consulting the tea leaves.

Click to view image: '214687-genetics.jpg'

Added: Aug-17-2008 
By: allyssa
Tags: Genetics, science, ancestry
Views: 7571 | Comments: 4 | Votes: 0 | Favorites: 1 | Shared: 1 | Updates: 0 | Times used in channels: 1
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  • Interesting article. Thanks

    Posted Aug-17-2008 By 

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    • I guess it's only you and me who think that! :)

      Posted Aug-17-2008 By 

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    • agreed

      Posted Aug-17-2008 By 

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    • Naw, that was a good article - it's obvious to genecists but there's still this CW in the public that now HGC is complete we're a few years away from Gattaca. We're not, but that doesn't make genetic advancement any less interesting. This article speaks to that public CW.

      Posted Aug-18-2008 By 

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    • I would have read it sooner but I just got the interwebs back up at my new place yesterday :)

      This is good news to me. Diversity is key to any organism's survival. The fact that we are so diverse means that no single disease or superbug will be able to kill everyone. Somewhere out there lives the freak who is immune to the next pandemic, whatever it is.

      Posted Aug-19-2008 By 

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